Agile scores in MASLD and ALD: External validation and their utility in clinical algorithms.

BACKGROUND & AIMS: Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis (F4), respectively, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We independently validated the diagnostic accuracy of these scores in MASLD, alcohol-related liver disease (ALD) and chronic hepatitis B or C (CHB/C) and assessed them in clinical algorithms with FIB-4 and LSM. METHODS: We included 4,243 patients (MASLD: 912, ALD: 386, CHB: 597, CHC: 2,348) with LSM, liver biopsy and laboratory tests within 6 months. FIB-4, Agile 3+ and Agile 4 scores were calculated. RESULTS: For F≥3, the diagnostic accuracy of Agile 3+ and LSM were similar in MASLD (AUC: 0.86 vs. 0.86, p = 0.831) and ALD (0.92 vs. 0.94, p = 0.123). For cirrhosis, Agile 4 was similar to LSM in MASLD (0.89 vs. 0.90, p = 0.412) and ALD (0.94 vs. 0.95, p = 0.513). Agile 3+/4 performed worse than LSM in CHB/C. Using predefined dual thresholds of 90% sensitivity/specificity, correct classification rates in MASLD were 66% vs. 61% using Agile 3+ vs. LS dual cut-offs and 71% vs. 67% in ALD, respectively. When using Agile 3+ or LSM as a second step after FIB-4 >1.3, correct classification rates were higher with Agile 3+ than LSM, both for MASLD (75% vs. 71%) and ALD (76% vs. 72%), with fewer indeterminate results. Positive agreement of LSM and Agile 3+/4 significantly increased the specificity of a diagnosis of advanced fibrosis/cirrhosis. CONCLUSION: Agile 3+ and Agile 4 have equal diagnostic accuracy with LSM in both MASLD and ALD but result in fewer indeterminate results. Sequential use of FIB-4 and Agile 3+/4 or concurrent Agile 3+/4 and LSM can be used to further optimize F≥3 diagnosis. IMPACT AND IMPLICATIONS: As of today, it is accepted that there will be no single non-invasive test or an isolated cut-off for identifying patients with advanced chronic liver disease. Here, we confirmed that Agile 3+ and Agile 4 scores are useful alternatives to simple liver stiffness measurement in diagnosing advanced fibrosis/cirrhosis in steatotic liver disease, but they do not perform as well in chronic viral hepatitis. Agile scores can help optimize the diagnosis of advanced fibrosis/cirrhosis in a dual cut-off strategy by reducing the number of indeterminate results either alone or in a sequential strategy after FIB-4. The combination of Agile scores and liver stiffness measurement can further increase our confidence in a positive diagnosis of advanced fibrosis/cirrhosis. These novel combination strategies can be useful tools to predict the likelihood of advanced stages of liver disease with the highest possible accuracy in a secondary/tertiary healthcare setting.

Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure.

BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed patients with cACLD (LSM ≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV cure by interferon-free therapies from 15 European centres. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: A total of 2,335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1,002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM change of -5.3 (-8.8 to -2.4) kPa corresponding to -33.9 (-48.0 to -15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p <0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5-year cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5-year cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM decrease of ≥20% (p = 0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. IMPACT AND IMPLICATIONS: Liver stiffness measurement (LSM) is increasingly applied as a prognostic biomarker and commonly decreases in patients with compensated advanced chronic liver disease achieving HCV cure. Although Baveno VII proposed criteria for a clinically significant decrease, little is known about the prognostic utility of LSM dynamics (changes through antiviral therapy). Interestingly, in those with a post-treatment LSM of 10-19.9 kPa, LSM dynamics did not provide incremental information, arguing against the consideration of LSM dynamics as prognostic criteria. Thus, post-treatment LSM should guide the management of patients with compensated advanced chronic liver disease achieving HCV cure.

Liver Stiffness Determined by Transient Elastography Is a Simple and Highly Accurate Predictor for Presence of Liver Cirrhosis in Clinical Routine.

INTRODUCTION: Early detection of patients with advanced chronic liver disease is critical for the prevention of complications and inclusion in surveillance programs for hepatocellular carcinoma. In daily clinical care, it remains challenging to differentiate early cirrhosis from lower fibrosis grades without performing a liver biopsy. The aim of the present study was to assess the performance of different non-invasive detection tools to differentiate cirrhosis from lower fibrosis grades. METHODS: Data of 116 patients (51 male, 65 female) with chronic liver disease of various origins undergoing liver biopsy was analyzed. Routine laboratory values, liver stiffness measurement (LSM) by transient elastography, and histological liver assessment were collected. RESULTS: Robust and significant correlations with the histological fibrosis stage were identified for LSM (r = 0.65), the FAST score (0.64), the FIB-4 (0.48), serum aspartate aminotransferase (AST) concentration (0.41), NFS (0.33), international normalized ratio (INR; 0.30), methacetin breath test results (-0.40), and serum albumin concentration (-0.29) by spearman rank correlation. Receiver operating characteristic curves were built for these parameters to separate patients with cirrhosis from those with any other fibrosis stage. The highest AUC was achieved by LSM (0.9130), followed by the FAST score (0.8842), the FIB-4 (0.8644), the NFS (0.8227), INR (0.8142), serum albumin (0.7710), and serum AST (0.7620). The most promising clinical applicability would be an LSM value of 12.2 kPa, achieving 95.7% sensitivity and 75.3% specificity. CONCLUSION: LSM and FAST score seem to be robust non-invasive measurements for liver fibrosis. LSM and FAST scores may have the potential to reliably detect patients with liver cirrhosis in clinical routine settings.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

BACKGROUND AND AIM: Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS: This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS: Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS: Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

Assessment of the Performance of Non-invasive Criteria for the Evaluation of Clinically Significant Portal Hypertension in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Assessment of clinically significant portal hypertension (CSPH) non-invasively using a combination of liver stiffness measurement (LSM) and platelet counts is proposed as an alternative to hepatic venous pressure gradient (HVPG) estimation. Utility of these criteria in compensated advanced chronic liver disease (cACLD) patients of different etiologies including nonalcoholic steatohepatitis (NASH) with BMI  >  30 kg/m2 was studied in a large cohort. METHODS: Consecutive patients of cACLD with available anthropometric and laboratory details, LSM, and HVPG were included in a retrospective analysis. A LSM of ≥ 25 kPa alone and LSM ≤ 15 kPa plus platelets ≥ 150 × 109/L were evaluated as non-invasive rule-in and rule-out criteria for CSPH, respectively. The NASH-ANTICPATE model (composite of BMI, platelets, and LSM) was evaluated in patients with obese NASH. RESULTS: Patients with cACLD (n = 626) (mean age: 50.8 ± 12.4 years, 74.2% males) with alcohol (ALD, 30.3%), NASH (26.4%), hepatitis C (HCV, 16.6%), hepatitis B (HBV,10.2%) etiology were included. The prevalence of CSPH was  >  80% across all etiologies except in HBV (62.5%) and in obese non-NASH (71-72%). The rule-in criteria had a PPV  >  90% for all etiologies except in HBV (80.8%). The rule-out criteria had a negative predictive value (NPV) of 65%, 53%, and 40% in ALD, HCV, and NASH, respectively. The NASH-ANTCIPATE model had specificity of 100% and NPV of 33% to detect CSPH in obese NASH (n = 62). CONCLUSIONS: LSM ≥ 25 kPa predicted CSPH in most etiologies except HBV. A significant proportion of patients have CSPH despite satisfying the rule-out criteria. The NASH-ANTICIPATE model is specific but fails to exclude CSPH in nearly two-third patients with obesity and NASH. There is a need for precise disease-specific non-invasive models for detecting CSPH.

[Baveno VII - Renewing consensus in portal hypertension: personalized care for portal hypertension].

The Baveno VII workshop held in October 2021 was featured by the subject of personalized care in portal hypertension. The workshop focused on the following 9 topics including: the relevance and indications for measuring the hepatic venous pressure gradient as a gold standard; the use of non-invasive tools for the diagnosis of compensated advanced chronic liver disease and clinically significant portal hypertension; the impact of etiological and of non-etiological therapies in the course of cirrhosis; the prevention of the first episode of decompensation; the management of the acute bleeding episode; the prevention of further decompensation; as well as the diagnosis and management of splanchnic vein thrombosis and other vascular disorders of the liver. This essay provides a compilation and summary of recommendations regarding the abovementioned topics, and presents the most recent research proceedings and the corresponding consensus to our readers.

Are we missing varices by implementing Baveno-VI recommendation of not screening patients with Compensated Advanced Chronic Liver Disease?

OBJECTIVES: This study aimed to validate Baveno-VI recommendations for variceal screening in cACLD in our region and proposed our own cutoff values. METHODS: Prospective cross-sectional study was conducted on cACLD patients from August 2020 till April 2021. Patients segregated into Group-A, having Liver stiffness measurement (LSM) of ≥ 20 kPa and platelet of ≤ 150 × 109 cells/L; and Group-B having LSM of < 20 kPa and PLT of > 150 × 109 cells/L. Gastroscopic findings were segregated into three categories, VNT, Varices Not Needing Treatment (VNNT) and No Varix (NV). ROC plots were generated for LSM and Platelet for VNT for sensitivity, specificity, Negative and Positive Predictive Values were calculated. RESULTS: A total of 134 patients of cACLD were included. Group-A had 72 (53.7%) patients and Group-B had 62 (46.3%) patients. Group-A had 6 (8.3%) NV; 18 (25.0%) VNNT and 48 (66.7%) VNT. Group-B had 26 (41.9%) NV, 24 (38.7%) VNNT and 12 (19.4%) VNT. The sensitivity of 66.7%, specificity of 80.6% and NPV of 67.56% was obtained. Thus 19.4% VNT were missed on following Baveno VI recommendations. ROC in our study suggested cutoff value of 11.5 kPa with sensitivity of 100% and 1-sepcifity pf 78% (AUROC = 0.865; p < .001) of LSM below which screening gastroscopy could be avoided. The positive and negative predicted values for 84.85% and 100% respectively. Cut off value of platelet count for VNNT came out to be ≥ 97.5 × 109 cells/L with AUROC 0.891 (p < .001), having sensitivity of 100 % and 1-specificity of 83.3%. CONCLUSIONS: Substantial number of VNT in cACLD patients are missed by following Baveno-VI recommendations and these needs to be revised on regional basis.

Development and validation of a radiomics signature as a non-invasive complementary predictor of gastroesophageal varices and high-risk varices in compensated advanced chronic liver disease: A multicenter study.

BACKGROUND AND AIM: Gastroesophageal varices (GEV) present in compensated advanced chronic liver disease (cACLD) and can develop into high-risk varices (HRV). The gold standard for diagnosing GEV is esophagogastroduodenoscopy (EGD). However, EGD is invasive and less tolerant. This study aimed to develop and validate radiomics signatures based on noncontrast-enhanced computed tomography (CT) images for non-invasive diagnosis of GEV and HRV in patients with cACLD. METHODS: The multicenter trial enrolled 161 patients with cACLD from six university hospitals in China between January 2015 and September 2019, who underwent both EGD and noncontrast-enhanced CT examination within 14 days prior to the endoscopy. Two radiomics signatures, termed rGEV and rHRV, respectively, were built based on CT images in a training cohort of 129 patients and validated in a prospective validation cohort of 32 patients (ClinicalTrials. gov identifier: NCT03749954). RESULTS: In the training cohort, both rGEV and rHRV exhibited high discriminative abilities on determining the existence of GEV and HRV with the area under receiver operating characteristic curve (AUC) of 0.941 (95% confidence interval [CI] 0.904-0.978) and 0.836 (95% CI 0.766-0.905), respectively. In validation cohort, rGEV and rHRV showed high discriminative abilities with AUCs of 0.871 (95% CI 0.739-1.000) and 0.831 (95% CI 0.685-0.978), respectively. CONCLUSIONS: This study demonstrated that rGEV and rHRV could serve as the satisfying auxiliary parameters for detection of GEV and HRV with good diagnostic performance.

Development of a machine learning model to predict bleed in esophageal varices in compensated advanced chronic liver disease: A proof of concept.

BACKGROUND AND AIM: Risk stratification beyond the endoscopic classification of esophageal varices (EVs) to predict first episode of variceal bleeding (VB) is currently limited in patients with compensated advanced chronic liver disease (cACLD). We aimed to assess if machine learning (ML) could be used for predicting future VB more accurately. METHODS: In this retrospective analysis, data from patients of cACLD with EVs, laboratory parameters and liver stiffness measurement (LSM) were used to generate an extreme-gradient boosting (XGBoost) algorithm to predict the risk of VB. The performance characteristics of ML and endoscopic classification were compared in internal and external validation cohorts. Bleeding rates were estimated in subgroups identified upon risk stratification with combination of model and endoscopic classification. RESULTS: Eight hundred twenty-eight patients of cACLD with EVs, predominantly related to non-alcoholic fatty liver disease (28.6%), alcohol (23.7%) and hepatitis B (23.1%) were included, with 455 (55%) having the high-risk varices. Over a median follow-up of 24 (12-43) months, 163 patients developed VB. The accuracy of machine learning (ML) based model to predict future VB was 98.7 (97.4-99.5)%, 93.7 (88.8-97.2)%, and 85.7 (82.1-90.5)% in derivation (n = 497), internal validation (n = 149), and external validation (n = 182) cohorts, respectively, which was better than endoscopic classification [58.9 (55.5-62.3)%] alone. Patients stratified high risk on both endoscopy and model had 1-year and 3-year bleeding rates of 31-43% and 64-85%, respectively, whereas those stratified as low risk on both had 1-year and 3-year bleeding rates of 0-1.6% and 0-3.4%, respectively. Endoscopic classification and LSM were the major determinants of model's performance. CONCLUSION: Application of ML model improved the performance of endoscopic stratification to predict VB in patients with cACLD with EVs.

Non-invasive prediction of liver-related events in patients with HCV-associated compensated advanced chronic liver disease after oral antivirals.

BACKGROUND & AIMS: It is important to know which patients with hepatitis C are likely to develop liver-related complications after achieving a sustained virological response (SVR) to direct-acting antiviral (DAA) therapy. We aimed to describe the incidence of liver-related events in a population of patients with HCV-associated compensated advanced chronic liver disease (cACLD) who achieved SVR and to identify non-invasive parameters that predict the occurrence of liver-related events. METHODS: This 2-center prospective study included 572 patients with cACLD who had been treated with DAAs and had achieved SVR. Patients had liver stiffness measurement (LSM) ≥10 kPa at baseline and had never decompensated (Child-Pugh class A). Laboratory work-up and LSM were performed at baseline and at 1 year of follow-up. RESULTS: The median follow-up was 2.8 years during which 32 patients (5.6%) presented with a liver-related event. The incidence rate (IR) of portal hypertension-related decompensation was 0.34/100 patient-years. These patients all had baseline LSM >20 kPa, and LSM did not improve during follow-up in 4 out of 5 of them. Hepatocellular carcinoma (HCC) occurred in 25 patients (IR 1.5/100 patient-years). Albumin levels at follow-up (hazard ratio [HR] 0.08; 95% CI 0.02-0.25) and LSM <10 kPa at follow-up (HR 0.33; 95% CI 0.11-0.96) were independently associated with the risk of HCC. Combining both predictors identified 2 groups with differing risk of HCC occurrence: those with LSM ≥20 kPa at follow-up or those with LSM between 10-20 kPa and albumin levels <4.4 g/dl were at the highest risk (IR ≥1.9/100 patient-years). Visual nomograms predicting HCC risk based on LSM and albumin at 1 year of follow-up were constructed. CONCLUSION: In patients with HCV-related cACLD who have achieved SVR with DAAs, HCC is the most frequent liver-related event. Both albumin levels and LSM are useful for stratifying patients based on their risk of developing HCC during follow-up. LAY SUMMARY: New oral antivirals can cure chronic hepatitis C infection, however patients with advanced chronic liver disease are still at risk of presenting with liver-related complications. The most frequent complication after oral antiviral therapy in asymptomatic patients with advanced chronic liver disease was liver cancer. The use of simple parameters such liver stiffness and albumin levels after treatment can help to identify patients at higher or lower risk of liver cancer.

2D shear wave liver elastography by Aixplorer to detect portal hypertension in cirrhosis: An individual patient data meta-analysis.

BACKGROUND & AIMS: Liver stiffness measured with 2-dimensional shear wave elastography by Supersonic Imagine (2DSWE-SSI) is well-established for fibrosis diagnostics, but non-conclusive for portal hypertension. METHODS: We performed an individual patient data meta-analysis of 2DSWE-SSI to identify clinically significant portal hypertension (CSPH), severe portal hypertension and large varices in cirrhosis patients, using hepatic venous pressure gradient and upper endoscopy as reference. We used meta-analytical integration of diagnostic accuracies with optimized rule-out (sensitivity-90%) and rule-in (specificity-90%) cut-offs. RESULTS: Five studies from seven centres shared data on 519 patients. After exclusion, we included 328 patients. Eighty-nine (27%) were compensated and 286 (87%) had CSPH. 2DSWE-SSI < 14 kPa ruled out CSPH with a summary AUROC (sROC), sensitivity and specificity of 0.88, 91% and 37%, and correctly classified 85% of patients, with minimal between-study heterogeneity. The false negative rate was 60%, of which decompensated patients accounted for 78%. 2DSWE-SSI ≥ 32 kPa ruled in CSPH with sROC, sensitivity, specificity and correct classifications of 0.83, 47%, 89% and 55%. In a subgroup analysis, the 14 kPa cut-off showed consistent sensitivity and higher specificity for patients with compensated cirrhosis, without ascites, viral aetiology or BMI < 25 kg/m2 . 2DSWE-SSI ruled out severe portal hypertension and large varices with fewer correctly classified and lower sROC, and with minimal benefit for ruling in. CONCLUSION: Liver stiffness using 2-dimensional shear wave elastography below 14 kPa may be used to rule out clinically significant portal hypertension in cirrhosis patients, but this would need validation in populations of compensated liver disease. 2DSWE-SSI cannot predict varices needing treatment.

Controlled attenuation parameter does not predict hepatic decompensation in patients with advanced chronic liver disease.

BACKGROUND & AIMS: Assessment of hepatic steatosis by transient elastography (TE)-based controlled attenuation parameter (CAP) might predict hepatic decompensation. Therefore, we aimed to evaluate the prognostic value of CAP in patients with compensated advanced chronic liver disease (cACLD) and decompensated cirrhosis (DC). METHODS: A total of 430 patients who underwent TE (liver stiffness ≥10 kPa) and CAP measurements were included in this retrospective analysis. Half of patients (n = 189) underwent simultaneous HVPG measurement. In cACLD patients, first hepatic decompensation was defined by new onset of ascites, hepatic encephalopathy or variceal bleeding. In patients with DC, the following events were considered as further hepatic decompensation: requirement of paracentesis, admission for/development of grade 3/4 hepatic encephalopathy, variceal (re-)bleeding or liver-related death. RESULTS: First hepatic decompensation occurred in 25 of 292 (9%) cACLD patients, while 46 of 138 (33%) DC patients developed further hepatic decompensation during a median follow-up of 22 and 12 months respectively. CAP was not predictive of first (cACLD; per 10 dB/m; hazard ratio [HR]: 0.97, 95% confidence interval [95% CI]: 0.91-1.03, P = 0.321) or further hepatic decompensation (DC; HR: 0.99, 95% CI: 0.94-1.03, P = 0.554) in adjusted analysis. Using the well-established CAP cut-off of ≥248 dB/m for hepatic steatosis, the incidence of first (cACLD; P = 0.065) and further hepatic decompensation (DC; P = 0.578) was similar in patients with hepatic steatosis or without. Serum albumin levels (per mg/dL; HR: 0.83, 95% CI: 0.77-0.89, P < 0.001) and MELD-Na (per point; HR: 1.15, 95% CI: 1.04-1.28, P = 0.006) in cACLD and MELD-Na (per point; HR: 1.12, 95% CI: 1.05-1.19, P < 0.0001) in DC patients were the only parameters independently associated with first and further hepatic decompensation, respectively. CONCLUSION: Controlled attenuation parameter does not predict the development of first (cACLD)/further (DC) hepatic decompensation, while serum albumin levels and MELD-Na are of prognostic value.

Validation of noninvasive methods to predict the presence of gastroesophageal varices in a cohort of patients with compensated advanced chronic liver disease.

BACKGROUND AND AIM: The aim was to validate noninvasive methods to predict the presence of gastroesophageal varices (GEV) in patients with suspected compensated advanced chronic liver disease. METHODS: We retrospectively reviewed clinical and radiological data collected prospectively between September 2013 and September 2015. We reviewed 442 consecutive patients with suspected compensated advanced chronic liver disease measured by transient elastography (TE) and a gastroscopy. We evaluated platelets, spleen diameter, TE, liver stiffness × spleen size/platelets (LSPS), variceal risk index (VRI), Baveno VI strategy, and Augustin algorithm. RESULTS: One hundred sixty-one out of 442 patients were included. Patients with GEV were compared with patients without GEV and showed statistically significant differences in platelet count (117 SD 51 vs 149 SD 62; P = 0.02), spleen diameter (13.0 SD 1.9 vs 11.5 SD 2; P = 0.003), and TE (28 SD 15 vs 19 SD 10; P = 0.001). Single methods (platelet count and TE) diagnosed correctly 51% and 71.4% of patients. Combined methods (LSPS, VRI, Baveno VI, and Augustin algorithm) diagnosed correctly 78%, 83.6%, 45.3%, and 57.1% of patients. Patients with GEV misdiagnosed: platelets 5/161 (3.1%), TE 6/161 (3.7%), LSPS 16/159 (10%), VRI 18/159 (11.3%), Baveno VI 3/161 (1.8%), and Augustin algorithm 6/161 (3.7%). Rate of unnecessary gastroscopies: platelets 46%, TE 25%, LSPS 13%, VRI 6%, Baveno VI 53%, and Augustin algorithm 39.1%. CONCLUSIONS: A significant number of patients were classified correctly using TE, LSPS, and VRI; however, LSPS and VRI had unacceptable rates of misdiagnoses. TE is the best noninvasive single method and the Baveno VI strategy the best combined method.

Noninvasive Assessment of Portal Hypertension.

The progressive use of noninvasive tests (NITs) has changed the way hepatologists diagnose and manage patients with chronic liver disease, mainly because of their easiness to use and the ability to be repeated during follow-up. Liver stiffness measurement is the NIT with more scientific evidence. NITs have demonstrated to be useful to detect not only liver fibrosis but also the presence of clinically significant portal hypertension. Moreover, current evidence supports they can also be useful to evaluate the prognosis of patients with chronic liver disease.

Psoas muscle area as a predictor of low muscle mass in Asian patients with compensated advanced chronic liver disease.

PURPOSE: The relationship between the psoas muscle index (PMI) and the appendicular skeletal muscle index (ASMI) in patients with compensated advanced chronic liver disease (cACLD) is not yet understood. Our goal is to determine which level of the lumbar spine best represents the appendicular skeletal muscle. METHODS AND MATERIALS: This retrospective study involved patients with cACLD between January 2020 and December 2021. We documented the patients' body weight, height, gait speed, handgrip strength, appendicular skeletal muscle measured by DXA, and psoas muscle area segmented on computed tomography or magnetic resonance imaging. Low muscle mass, as defined by the Asian working group for sarcopenia, is less than 7.0 kg/m2 in males and less than 5.4 kg/m2 in females. We analyzed the correlation between PMI and ASMI. RESULTS: A total of 134 patients were enrolled in the study, with 74 being male and 60 being female. The mean age was 63.9 ± 7.7 years old. Significant associations (p < 0.001) were found between PMI of all levels and ASMI. In the analysis of Pearson's correlation coefficients, it was noted that the r value increased gradually in both males (r = 0.3197 at L2, 0.4006 at L3, 0.5769 at L4) and females (r = 0.3771 at L2, 0.4557 at L3, 0.5251 at L4). Similarly, the area under the curve (AUC) values predicting low muscle mass were as follows: for males, AUC=0.582 at L2, 0.619 at L3, 0.728 at L4; for females, AUC=0.685 at L2, 0.733 at L3, 0.744 at L4. The cut-off point for PMI in males was 4.12 at L2, 6.25 at L3, and 8.48 at L4, while in females was 2.61 at L2, 4.47 at L3, 6.07 at L4. CONCLUSION: The Psoas muscle index can be used to assess the muscle mass status in patients with cACLD. Among the various levels that can be used, we recommend using the fourth inferior endplate of the lumbar spine, as it shows the highest correlation. Additionally, we suggest using a PMI cut-off point of 8.48 cm2/m2 for males and 6.07 cm2/m2 for females as a predictor of low muscle mass in Asian.

Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort. Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM). Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

The Story of Ammonia in Liver Disease: An Unraveling Continuum.

Hyperammonemia and liver disease are closely linked. Most of the ammonia in our body is produced by transamination and deamination activities involving amino acid, purine, pyrimidines, and biogenic amines, and from the intestine by bacterial splitting of urea. The only way of excretion from the body is by hepatic conversion of ammonia to urea. Hyperammonemia is associated with widespread toxicities such as cerebral edema, hepatic encephalopathy, immune dysfunction, promoting fibrosis, and carcinogenesis. Over the past two decades, it has been increasingly utilized for prognostication of cirrhosis, acute liver failure as well as acute on chronic liver failure. The laboratory assessment of hyperammonemia has certain limitations, despite which its value in the assessment of various forms of liver disease cannot be negated. It may soon become an important tool to make therapeutic decisions about the use of prophylactic and definitive treatment in various forms of liver disease.